Diltiazem HCl suppresses porcine reproductive and respiratory syndrome virus infection in susceptible cells and in swine

》》文章原文链接：Diltiazem HCl suppresses porcine reproductive and respiratory syndrome virus infection in susceptible cells and in swine

》》Journal：Vet Microbiol . 

》》相关产品：Diltiazem hydrochloride (SJ-MX2584)

》》产品引用描述：

》》Abstract：

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen for swine, resulting in substantial economic losses to the swine industry. However, there has been little success in developing effective vaccines or drugs for PRRSV control. In the present study, we discovered that Diltiazem HCl, an inhibitor of L-type Ca²⁺ channel, effectively suppresses PRRSV replication in MARC-145, PK-15^CD163 and PAM cells in dose-dependent manner. Furthermore, it demonstrates a broad-spectrum activity against both PRRSV-1 and PRRSV-2 strains. Additionally, we explored the underlying mechanisms and found that Diltiazem HCl -induced inhibition of PRRSV associated with regulation of calcium ion homeostasis in susceptible cells. Moreover, we evaluated the antiviral effects of Diltiazem HCl in PRRSV-challenged piglets, assessing rectal temperature, viremia, and gross and microscopic lung lesions. Our results indicate that Diltiazem HCl treatment alleviates PRRSV-induced rectal temperature spikes, pulmonary pathological changes, and serum viral load. In conclusion, our data suggest that Diltiazem HCl could serve as a novel therapeutic drug against PRRSV infection.

》》部分实验数据展示：

Fig. 4. Diltiazem HCl inhibited other PRRSV-1 and PRRSV-2 strains infection The MARC-145 cells were incubated with the presence or absence of Diltiazem HCL (100 µM) for 1 h, infected with GZ-1101 or P3303 (MOI= 0.1) 1 h at 37 ℃ respectively. These cells were collected to measure PRRSV N protein expression in transcription levels via RT-qPCR (A), and in protein level by Western blot detection at 24 hpi (B). Subsequently, the antiviral activity of Diltiazem HCL against different PRRSV-1 strains was also checked in PAMs. These cells were collected to monitor PRRSV N gene expression at 24 hpi by RT-qPCR (C), and Western blot (D). The MARC-145 cells were incubated with the presence or absence of Diltiazem HCL (100 µM) for 1 h, infected with various PRRSV-2 strains (VR-2332, CH-1a, JXA1, and NADC30-like) at 0.1 MOI 1 h at 37 ℃ respectively. These cells were harvested to measure PRRSV N protein in transcription levels via RT-qPCR (E), in protein level by Western blot detection at 24 hpi (F). Subsequently, the antiviral effect of Diltiazem HCL against PRRSV-2 strains was also checked in PAM cells. N gene expression of PRRSV was monitored at 24 hpi by RT-qPCR (G), and Western blot (H).